The overall objectives of the proposed research are several: (1) a better understanding of the role of 3',5'-cyclic AMP (c-AMP) in malignant cell transformation; (2) an improved appreciation of the influence of ring geometry on the ease of microsomal oxidation and cytostatic activity of cyclophosphamide derivatives; (3) increased synthetic utilization of free radical chemistry and photochemistry of trivalent organophosphorus compounds. A thorough study of diastereoisomerism and conformation in the six-member ring of 3',5'-cyclic-AMP derivatized at phosphorus is planned. Effect of geometry on activity will be related in investigations of enzyme activity and in vivo potential against cancer. Similarly, we intend to develop new methods to determine ring conformation and substituent orientation in cyclophosphamides derivatized at the 4- and 5-carbons. Conformational effects will be related to ease of microsomal activation and to cytostatic activity. Certain free radical displacement reactions, which occur at trivalent phosphorus, will be studied stereochemically to increase our knowledge of the role of stereo and electronic effects on configuration of phosphoranyl radicals. Intramolecular cyclizations based on the above will be explored with a view toward synthetic applicability. New intramolecular photoreactions of keto-containing trivalent phosphorus compounds will be investigated in exploratory fashion for their synthetic potential and their mechanistic relation to free-radical models.